Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study
Chlamydia pneumoniae causes respiratory infection in adults and children, and has been associated with asthma exacerbations and induction of Immunoglobulin (Ig) E responses. We previously reported that C. pneumoniae enhances T helper (Th) 2 responses of peripheral blood mononuclear cells (PBMC) from asthmatic patients. It is likely that toll like receptor (TLR)-2 and TLR-4 mediate cytokine responses and host defense against C. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model.
PBMC (1.5 × 106) from asthmatic patients (N = 10) and non-asthmatic controls (N = 5) were infected or mock-infected for 1 h ± C. pneumoniae TW183 at a multiplicity of infection (MOI) = 1 and MOI = 0.1, and cultured for 48 h ± anti- TLR-2 and TLR-4 antibodies (Abs) (1 mg/mL). Interleukin (IL)-12 (48 h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA).
High IgE levels were detected in supernatants of C. pneumoniae- infected PBMC from asthmatics on day 10, compared with mock-infected PBMC (p < 0.03). In contrast, IgE was not detected (<0.3 ng/mL) in either C. pneumoniae infected or mock-infected PBMC from non-asthmatics. IL-12 production by C. pneumoniae-infected asthmatic and non-asthmatic PBMC were similar. When anti-TLR4, but not anti-TLR2, was included in culture, IL-12 production by C. pneumoniae- infected asthmatic PBMC decreased.
C. pneumoniae infection induces IgE production and modulates IL-12 responses in patients with asthma, which may be caused, in part, by differences in TLR-2 and TLR-4 stimulation.
KeywordsC. pneumoniae Interleukin-12 Asthma Toll like receptors
- C. pneumoniae
Peripheral blood mononuclear cells
Toll like receptor
Tumor necrosis factor alpha
Enzyme-linked immunosorbent assay
Pathogen-associated molecular patterns
We would like to thank Kevin B. Norowitz, M.D., Department of Pediatrics, SUNY Downstate Medical Center for fruitful discussions.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest to disclose.
Human and animal rights statement
Research involving human participants was approved by the SUNY Downstate Med Ctr IRB committee (stated in methods).
We had informed consent from patients.
This work was supported by the Thrasher Research Fund (Young Investigator Award awarded to Stephan Kohlhoff, M.D.) and a NY State Divisional Grant (Awarded to Tamar A. Smith-Norowitz, Ph.D).
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